ArticleEnvironmental health perspectives2025
Perinatal Exposure to Lead or Diethylhexyl Phthalate in Mice: Sex-Specific Effects on Cardiac DNA Methylation and Gene Expression across Time.
Article in Environmental health perspectives, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
4 citing papers in PubMed.
- From Exposure to Atherosclerosis: Mechanistic Insights into Phthalate-Driven Ischemic Heart Disease and Prevention Strategies.Life (Basel, Switzerland) · 2026Review
- Gut microbial metabolites in inflammatory bowel disease: immunological mechanisms regulating Treg/Th17 balance and therapeutic potential.Frontiers in immunology · 2026Review
- Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.Epigenetics · 2025Article
- Sexually dimorphic effects of in-utero exposure to a real-life environmental chemical mixture on markers of cardiovascular function in adult sheep.Environmental toxicology and pharmacology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundGlobal and site-specific changes in DNA methylation and gene expression are associated with cardiovascular development, aging, and disease, but how the transcriptome and epigenome of the heart change across the life course in males vs. females and how chemical exposures early in life influence this programming have not yet been investigated.
objectivesWe used an established mouse model of developmental exposures to investigate the effects of perinatal exposure to either lead (Pb) or diethylhexyl phthalate (DEHP), two ubiquitous environmental contaminants that are both strongly associated with cardiovascular diseases (CVDs), on DNA methylation and gene expression across the life course in whole hearts.
methodsDams were randomly assigned to receive human physiologically relevant levels of Pb (
resultsThousands of DMRs and hundreds of DEGs were identified in control, DEHP, and Pb-exposed hearts across time between 3 wk and 10 months of age. A closer look at the genes and pathways showing differential DNA methylation revealed that the majority were unique to each sex and exposure group. Overall, pathways governing development and differentiation changed across time in all conditions. A small number of genes in each group showed significant differences in DNA methylation and gene expression with life stage, including several that were different in toxicant-exposed but not control mice. We also observed subtle but significant differences in the proportion of several cell types that were associated with life stage, sex, or developmental exposure. DISCUSSION: Together these data suggest that gene expression and DNA methylation programs, as well as cellular composition, may differ across the life course long after cessation of exposure in perinatal Pb- or DEHP-exposed mice compared to controls and highlight potential biomarkers of developmental toxicant exposures; however, additional studies are required for confirmation. Further studies are also needed to investigate how epigenetic and transcriptional differences impact cardiovascular health across the life course, particularly in old age when the risk of cardiovascular diseases is markedly increased. https://doi.org/10.1289/EHP15503.
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Registered trials
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